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Pharmacology

DrugBank

State Solid

Description

Dronabinol (marketed as Marinol) is a synthetic form of delta-9-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component of cannabis (marijuana). THC demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, which results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. Due to its evidence as an appetite stimulant and an anti-nauseant, Dronabinol is approved for use in anorexia associated with weight loss in patients with AIDS and for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments . Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most abundant cannabinoids found naturally in the resin of the marijuana plant, both of which are pharmacologically active due to their interaction with cannabinoid receptors that are found throughout the body . While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. If not provided in their activated form (such as through synthetic forms like Dronabinol or DB00486), THC and CBD are obtained through conversion from their precursors, tetrahydrocannabinolic acid-A (THCA-A) and cannabidiolic acid (CBDA), through decarboxylation reactions.

Mechanism of Action

Dronabinol is a synthetic form of delta-9-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component of cannabis (marijuana). THC demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, which results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes.

Pharmacodynamics

Marinol may has complex effects on the central nervous system (CNS), including cannabinoid receptors. Dronabinol may inhibit endorphins in the emetic center, suppress prostaglandin synthesis, and/or inhibit medullary activity through an unspecified cortical action.

Metabolism

THC is primarily metabolized in the liver by microsomal hydroxylation and oxidation reactions catalyzed by Cytochrome P450 enzymes. 11-hydroxy-▵9-tetrahydrocannabinol (11-OH-THC) is the primary active metabolite, capable of producing psychological and behavioural effects, which is then metabolized into 11-nor-9-carboxy-▵ 9-tetrahydrocannabinol (THC-COOH), THC's primary inactive metabolite . Dronabinol and its principal active metabolite, 11-OH-delta-9-THC, are present in approximately equal concentrations in plasma. Concentrations of both parent drug and metabolite peak at approximately 0.5 to 4 hours after oral dosing and decline over several days .

Absorption

Dronabinol capsules are almost completely absorbed (90 to 95%) after single oral doses. Due to the combined effects of first pass hepatic metabolism and high lipid solubility, only 10 to 20% of the administered dose reaches the systemic circulation. After oral administration, dronabinol has an onset of action of approximately 0.5 to 1 hours and peak effect at 2 to 4 hours. Following BID dosing of 2.5mg of dronabinol, Cmax was found to be 1.32ng/mL with a median Tmax of 1.00 hr.

Indication

For the treatment of anorexia associated with weight loss in patients with AIDS, and nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments

Half-life

The elimination phase of dronabinol can be described using a two compartment model with an initial (alpha) half-life of about 4 hours and a terminal (beta) half-life of 25 to 36 hours.

Protein Binding

The plasma protein binding of dronabinol and its metabolites is approximately 97%.

Elimination

Dronabinol and its biotransformation products are excreted in both feces and urine. Because of its large volume of distribution, dronabinol and its metabolites may be excreted at low levels for prolonged periods of time. Following single dose administration, low levels of dronabinol metabolites have been detected for more than 5 weeks in the urine and feces.

Volume of Distribution

Dronabinol has a large apparent volume of distribution, approximately 10 L/kg, because of its lipid solubility.

Clearance

Values for clearance average about 0.2 L/kg-hr, but are highly variable due to the complexity of cannabinoid distribution.

Effect Profile

Curated + 94 Reports

Psychedelic 6.6

Strong visuals, body load, and auditory effects with mild headspace

Visual Intensity×3

1010

Headspace Depth×3

55.3

Auditory Effects×1

810

Body Load / Somatic Effects×1

106.3

Catalog Erowid

Stimulant 6.5

Strong stimulation, anxiety/jitters, and euphoria with low focus

Stimulation / Energy×3

105.8

Euphoria / Mood Lift×2

84.6

Focus / Productivity×2

34.9

Anxiety / Jitters×1

1010

Catalog Erowid

Based on reports from:

Effect Index Brief Unity on Weed — Maethor Erowid Experience Reports PsychonautWiki THC

Tolerance & Pharmacokinetics

drugs.wiki

Half-Life

≈ 1–3 days (occasional users), prolonged up to ~13 days with chronic use due to adipose redistribution

Addiction Potential

Low–moderate. Psychological dependence possible; physical dependence mild. Withdrawal typically irritability, sleep disturbance, decreased appetite.

Tolerance Decay

Full tolerance 10d Half tolerance 14d Baseline ~28d

Based on human imaging and clinical studies showing CB1 down‑regulation with daily use and reversal over days–weeks. Model is approximate and varies with dose, frequency, and route. Data quality: mixed clinical/anecdotal.

Cross-Tolerances

Other CB1‑active cannabinoids

50% ●●○

Experience Report Analysis

Erowid

94 Reports

1991–2025 Date Range

53 With Age Data

33 Effects Detected

Demographics

Gender Distribution

Age Distribution

Reports Over Time

Effect Analysis

Erowid

Effects aggregated from 94 experience reports (94 Erowid)

94 Reports

33 Effects Detected

12 Positive

13 Adverse

8 Neutral

Effect Sentiment Distribution

Confidence Distribution

Positive Effects 12

Anxiety Suppression 47.9% 70%

Music Enhancement 38.3% 70%

Stimulation 34.0% 70%

Color Enhancement 31.9% 70%

Euphoria 30.9% 70%

Empathy 25.5% 70%

Focus Enhancement 24.5% 70%

Sedation 22.3% 70%

Tactile Enhancement 17.0% 70%

Body High 11.7% 70%

Introspection 8.5% 70%

Creativity Enhancement 4.3% 70%

Adverse Effects 13

Confusion 29.8% 70%

Nausea 26.6% 70%

Memory Suppression 8.5% 70%

Muscle Tension 6.4% 70%

Motor Impairment 6.4% 70%

Increased Heart Rate 6.4% 70%

Jaw Clenching 5.3% 70%

Headache 4.3% 70%

Psychosis 4.3% 70%

Sweating 4.3% 70%

Seizure 4.3% 70%

Appetite Suppression 3.2% 70%

Thought Loops 3.2% 70%

Dosage Distribution

Dose distribution from experience reports

Median: 10.0 mg IQR: 5.0–20.0 mg n=11

Real-World Dose Distribution

62K Doses

From 28 individual dose entries

Oral (n=23)

Median: 10.0mg 25th: 5.0mg 75th: 10.0mg 90th: 19.0mg

mg/kg median: 0.122 mg/kg 75th: 0.186

Common Combinations

Most co-occurring substances in experience reports

Form / Preparation

Most common forms and preparations reported

Body-Weight Dosing

Dose relative to body weight from reports with weight data

Median: 0.184 mg/kg IQR: 0.074–0.294 mg/kg n=11

Redose Patterns

Redosing behavior across 21 reports

9.5% Redosed

1.1 Avg Doses

60m Median Interval

Harm Reduction

drugs.wiki

Harm‑reduction additions and clarifications:

• “Start low, go slow,” especially with edibles: Oral THC has low/variable bioavailability and first‑pass conversion to 11‑hydroxy‑THC, which is more psychoactive and longer‑acting. Wait at least 2 hours before considering redosing to avoid delayed over‑intoxication. High‑fat meals can significantly increase oral THC exposure.

• Driving: Simulator and epidemiologic data indicate meaningful impairment for several hours after use, often beyond users’ self‑perception. Avoid driving or operating hazardous machinery for a minimum of 4–6 hours after inhalation and longer after higher oral doses; co‑use with alcohol markedly magnifies crash risk. THC can remain detectable long after impairment has resolved, especially in frequent users.

• Inhaled vapes: Avoid illicit/counterfeit THC cartridges; vitamin E acetate and other diluents were strongly linked to EVALI cases in 2019. Prefer regulated, tested products if vaping at all.

• Cannabinoid Hyperemesis Syndrome (CHS): Chronic, heavy use can cause cyclic vomiting relieved by hot showers; topical capsaicin may help acutely, but complete cessation is the definitive treatment.

• Cardiovascular and orthostatic effects: THC can cause tachycardia and vasodilation with orthostatic hypotension; people with significant cardiovascular disease should avoid or minimize THC.

• Mental health: Higher‑THC exposure, early onset, and heavy/frequent use are associated with increased risk of anxiety symptoms and psychotic‑like experiences; avoid if you have a personal or strong family history of psychosis, and prefer lower‑THC/higher‑CBD products if using.

• Adolescents/young adults: Because brains are still developing, initiate use later if at all; frequent adolescent use is linked to worse mental‑health and cognitive outcomes.

• Pregnancy and lactation: Avoid cannabis/CBD during pregnancy and while breastfeeding. THC crosses the placenta and is excreted into breast milk for days to weeks; potential neurodevelopmental risks are uncertain but concerning.

• Storage and pediatric safety: Edibles are a common source of accidental pediatric intoxication; store products in child‑resistant containers, locked and out of sight.

• Product variability: Non‑prescription CBD products and some cannabis edibles can be mislabeled for potency and purity; use lab‑tested, regulated sources when possible.

• Tolerance: With frequent use, CB1 down‑regulation produces tolerance to many subjective effects; tolerance reverses over days to weeks of abstinence, which also reduces withdrawal symptoms (sleep disturbance, irritability, appetite change).

• Genetics/phenoconversion: CYP2C9 poor metabolizers, or those taking CYP2C9 inhibitors, may experience stronger/longer effects from oral THC; start with lower doses.

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